Single high-fat challenge and trained innate immunity: A randomized controlled cross-over trial
Brief exposure of monocytes to atherogenic molecules, such as oxidized lipoproteins, triggers a persistent pro-inflammatory phenotype, named trained immunity. In mice, transient high-fat diet leads to trained immunity, which aggravates atherogenesis. We hypothesized that a single high-fat challenge in humans induces trained immunity. In a randomized controlled cross-over study, 14 healthy individuals received a high-fat or reference shake, and blood was drawn before and after 1, 2, 4, 6, 24, and 72 h. Incubation of donor monocytes with the post-high-fat-shake serum induced trained immunity, regulated via Toll-like receptor 4. This was not mediated via triglyceride-rich lipoproteins, C12, 14, and 16, or metabolic endotoxemia. <i>In vivo</i>, however, the high-fat challenge did not affect monocyte phenotype and function. We conclude that a high-fat challenge leads to alterations in the serum composition that have the potential to induce trained immunity <i>in vitro</i>. However, this does not translate into a (persistent) hyperinflammatory monocyte phenotype <i>in vivo</i>.
Authors
- Martin Giera (ORCID: https://orcid.org/0000-0003-1684-1894)
- Siroon Bekkering (ORCID: https://orcid.org/0000-0003-1149-466X)
- Leo A. B. Joosten (ORCID: https://orcid.org/0000-0001-6166-9830)
- Julia van Tuijl (ORCID: https://orcid.org/0000-0001-8042-6121)
- Niels Peter Riksen (ORCID: https://orcid.org/0000-0001-9197-8124)
- Wieteke Broeders (ORCID: https://orcid.org/0000-0002-6466-8937)
- Johan Wijma
- Julia I. P. van Heck (ORCID: https://orcid.org/0000-0002-6929-9624)
- Lydia A. Afman (ORCID: https://orcid.org/0000-0002-7939-6217)
- Harsh Bahrar (ORCID: https://orcid.org/0000-0002-7686-4281)
- Yvonne M. ten Have
- Laura Rodwell (ORCID: https://orcid.org/0000-0002-5635-4997)
- Heidi Zweers-van Essen
- Mihai G. Netea (ORCID: https://orcid.org/0000-0003-2421-6052)
Institutions
- Royal Children's Hospital (AU)
- University of Bonn (DE)
- Radboud University Nijmegen (NL)
- Iuliu Hațieganu University of Medicine and Pharmacy (RO)
- Leiden University Medical Center (NL)
- Radboud University Medical Center (NL)
- Murdoch Children's Research Institute (AU)
- Wageningen University & Research (NL)
Publication Details
- Journal
- iScience
- Published
- 2024-10-04
- DOI
- https://doi.org/10.1016/j.isci.2024.111103
- Citations
- 4
- Primary Topic
- Immune responses and vaccinations
- Type
- article
- Field-Weighted Citation Impact
- 0.96
Funders
- Dutch Cardiovascular Alliance
- Hartstichting
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- European Research Area Network on Cardiovascular Diseases
- European Research Council
- FP7 Ideas: European Research Council